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Spark of life: Metabolism appears in lab without cells

By Linda Geddes

LIFE doesn’t have to be complex. The metabolic processes that underpin life on Earth have arisen spontaneously outside cells.

The cascade of reactions known as metabolism happens in all cells, providing them with the raw materials they need to survive. The serendipitous finding that many of these reactions can occur in simple conditions gives fresh insights into life’s beginnings. It also suggests that the complex processes needed for life may have surprisingly humble origins.

“People have said these pathways look so complex that they couldn’t form by environmental chemistry alone,” says Markus Ralser of the University of Cambridge, who led the research.

But the findings suggest many of these reactions could have occurred spontaneously in Earth’s early oceans, catalysed by metal ions rather than the enzymes that drive them in cells today.

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The origin of metabolism is a major gap in our understanding of the emergence of life. “Around the world, this network of reactions always looks very similar, suggesting that it must have come into place very early on in evolution, but no one knew when or how,” says Ralser.

One theory is that RNA was the first building block of life, because it helps to produce the enzymes that catalyse complex reactions. Another possibility is that metabolism came first. It may even have generated the molecules needed to make RNA, and cells could have incorporated these processes later. However, there was little evidence to support this idea.

“This is the first experiment showing that it is possible to create metabolic networks in the absence of RNA,” Ralser says.

Remarkably, the discovery was an accident. Rasler’s team was carrying out routine tests of the medium they use to culture cells, when a student decided to run unused samples through a mass spectrometer as a shortcut. This detected a signal for pyruvate – an end product of a metabolic pathway called glycolysis.

To test whether a similarly spontaneous process could have helped to spark life on Earth, the team approached colleagues in the earth sciences department who had been working on reconstructing the chemistry of the Archean Ocean. This ocean covered the planet almost 4 billion years ago – a time before photosynthesis when the world was oxygen-free and waters were rich in iron, as well as other metals and phosphate. All these substances could potentially aid chemical reactions like the ones seen in modern cells.

Ralser’s team took early-ocean solutions and added substances known to be starting points of modern metabolic pathways. They heated the samples to between 50 °C and 70 °C – the sort of temperatures you might find near a hydrothermal vent – for 5 hours. They then analysed the solution to see what molecules were present.

“We had hoped to find one reaction or two maybe, but the results were amazing,” says Ralser. “We could reconstruct two metabolic pathways almost entirely.”

The pathways were glycolysis and the pentose phosphate pathway, “reactions that form the core metabolic backbone of every living cell”, Ralser adds.

Together, these pathways produce some of the most important materials in cells, including ATP – which gives cells energy – as well as the sugars that form DNA and RNA, and the molecules needed to make fats and proteins.

If these metabolic pathways occurred in the early oceans, the first cells could have enveloped them as they developed membranes.

The first cells could have enveloped these pathways as they developed membranes

In all, 29 metabolism-like chemical reactions were spotted, seemingly catalysed by iron and other metals that would have been found in early ocean sediments. The metabolic pathways found aren’t identical to modern ones, but many of the same molecules are formed, says Ralser. These pathways could have been refined after enzymes evolved inside cells.

Ralser thinks that detecting the metabolite ribose 5-phosphate is particularly noteworthy. This is because it is a precursor to RNA, which encodes information, catalyses chemical reactions and, most importantly, can replicate.

“This paper has really interesting connotations for the origins of life,” says Matthew Powner at University College London. It hints at how more complex enzymes could have evolved, he says, because substances that made these early processes more efficient would have been favoured.

One potential flaw in the idea is that the reactions seen so far only go in one direction; from complex sugars to simpler molecules such as pyruvate. “Given the data, one might well conclude that any organics in the ocean would have been totally degraded, rather than forming the basis of modern metabolism,” says Jack Szostak at Harvard University. “I would conclude that metabolism had to evolve, within cells, one reaction and one catalyst at a time.”

But Ralser disagrees. However the reaction is catalysed, it leads to the same result, he says. “Every chemical reaction is in principle reversible, whether an enzyme or a simple molecule is the catalyst.”

This article appeared in print under the headline “Metabolism sparks in lab without cells”